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Although incurable pathologies associated with the formation of highly ordered fibrillar protein aggregates called amyloids have been known for about two centuries, functional roles of amyloids have been studied for only two decades. Recently, we identified functional amyloids in plants. These amyloids formed using garden pea Pisum sativum L. storage globulin and vicilin, accumulated during the seed maturation and resisted treatment with gastric enzymes and canning. Thus, vicilin amyloids ingested with food could interact with mammalian proteins. In this work, we analyzed the effects of vicilin amyloids on the fibril formation of proteins that form pathological amyloids. We found that vicilin amyloids inhibit the fibrillogenesis of these proteins. In particular, vicilin amyloids decrease the number and length of lysozyme amyloid fibrils; the length and width of β-2-microglobulin fibrils; the number, length and the degree of clustering of β-amyloid fibrils; and, finally, they change the structure and decrease the length of insulin fibrils. Such drastic influences of vicilin amyloids on the pathological amyloids’ formation cause the alteration of their toxicity for mammalian cells, which decreases for all tested amyloids with the exception of insulin. Taken together, our study, for the first time, demonstrates the anti-amyloid effect of vicilin fibrils and suggests the mechanisms underlying this phenomenon.

Piscirickettsia salmonis is the pathogen that most affects the salmon industry in Chile. Large quantities of antibiotics have been used to control it. In search of alternatives, we have developed [Cu(NN[sub.1])[sub.2]]ClO[sub.4] where NN[sub.1] = 6-((quinolin-2-ylmethylene)amino)-2H-chromen-2-one. The antibacterial capacity of [Cu(NN[sub.1])[sub.2]]ClO[sub.4] was determined. Subsequently, the effect of the administration of [Cu(NN[sub.1])[sub.2]]ClO[sub.4] on the growth of S. salar, modulation of the immune system and the intestinal microbiota was studied. Finally, the ability to protect against a challenge with P. salmonis was evaluated. The results obtained showed that the compound has an MIC between 15 and 33.9 μg/mL in four isolates. On the other hand, the compound did not affect the growth of the fish; however, an increase in the transcript levels of IFN-γ, IL-12, IL-1β, CD4, lysozyme and perforin was observed in fish treated with 40 μg/g of fish. Furthermore, modulation of the intestinal microbiota was observed, increasing the genera of beneficial bacteria such as Lactobacillus and Bacillus as well as potential pathogens such as Vibrio and Piscirickettsia. Finally, the treatment increased survival in fish challenged with P. salmonis by more than 60%. These results demonstrate that the compound is capable of protecting fish against P. salmonis, probably by modulating the immune system and the composition of the intestinal microbiota.

Deep-learning language models have shown promise in various biotechnological applications, including protein design and engineering. Here we describe ProGen, a language model that can generate protein sequences with a predictable function across large protein families, akin to generating grammatically and semantically correct natural language sentences on diverse topics. The model was trained on 280 million protein sequences from >19,000 families and is augmented with control tags specifying protein properties. ProGen can be further fine-tuned to curated sequences and tags to improve controllable generation performance of proteins from families with sufficient homologous samples. Artificial proteins fine-tuned to five distinct lysozyme families showed similar catalytic efficiencies as natural lysozymes, with sequence identity to natural proteins as low as 31.4%. ProGen is readily adapted to diverse protein families, as we demonstrate with chorismate mutase and malate dehydrogenase. A generative deep-learning model designs artificial proteins with desired enzymatic activities.

In the article, a simple and label-free strategy was proposed for the sensitive detection of lysozyme based on the fluorescence quenching of positively charged gold nanorods ((+)AuNRs) to DNA-templated silver nanoclusters (DNA/AgNCs). To construct the sensor, a DNA template was designed with a C-rich sequence at the 5′-terminal for the synthesis of AgNCs, while a lysozyme binding aptamer (LBA) at the 3′-terminal for the recognition of lysozyme, and such DNA/AgNCs was used as the fluorescence probe. Meantime, the fluorescence signal of such DNA/AgNCs can be quenched based on the electrostatic adsorption of them with (+)AuNRs, due to the surface energy transfer. In the presence of lysozyme, the specific binding happened between the LBA section of DNA/AgNCs and lysozyme, inducing the reduction of the total charge of DNA/AgNCs and weakening the adsorption of them with (+)AuNRs, which directly resulting in the recovery of the fluorescence signal. Besides, the fluorescence signal recovery of DNA/AgNCs has a linear positive proportional relationship with lysozyme concentration in the range of 10 pM–2.0 nM under the optimal conditions. Moreover, a satisfactory recovery (99.6–107.2%) was obtained while detecting lysozyme in human serum samples.

Eggshell membrane (ESM) is composed of approximately 90% protein. Our previous studies in healthy adults demonstrated that two months of daily ESM intake improved respiratory function, zigzag walking speed, and skin elasticity. The present study aims to address the knowledge gap regarding the in vivo effects of ESM in the context of inflammatory bowel disease (IBD). Proteomic analysis was performed on powdered ESM used as a dietary supplement. To investigate its pharmacokinetics in mice, tritium ([sup.3]H)-labeled ESM was prepared using the [sup.6]Li(n,α)[sup.3]H nuclear reaction. The therapeutic potential of ESM was further examined in a 2.0% dextran sulfate sodium (DSS)-induced murine model of IBD. In addition, fecal samples from both mice and healthy human subjects were analyzed using a modified terminal restriction fragment length polymorphism (T-RFLP) method. Lysozyme C (LYZ) was the most abundant protein (47%), followed by lysyl oxidase (12%) in ESM used in this study. [sup.3]H-ESM was mixed with MediGel, and orally administered to mice. Radioactivity levels were measured in blood, organs (duodenum, small intestine, large intestine, liver, kidney, lung, skin), and rectal feces at 0.5, 2, 5, 24, 48, and 72 h post-administration. Radioactivity in feces indicated excretion of undigested components, while systemic distribution suggested potential whole-body effects of ESM. Oral ESM and LYZ significantly alleviated body weight loss, diarrhea, and hematochezia in a DSS-induced murine model of IBD, leading to a significantly lower disease activity index on day 3 and showing a similar trend on day 5. Gut microbiota analysis showed increased Bacteroidales in the DSS group, while the ESM + DSS group maintained levels similar to the control. In humans, a double-blind, randomized controlled trial was conducted to evaluate the effects of ESM on gut microbiota in healthy adults. Participants received either ESM or placebo for 8 weeks. revealed a significant increase in alpha diversity at weeks 1 and 8 in the ESM group (p < 0.05), with between-group differences evident from week 1 (p < 0.01). ESM intake reduced Bacteroides and significantly increased Bifidobacterium and Lactobacillales at weeks 4 and 8. These findings suggest ESM supplementation promotes beneficial modulation of gut microbiota. These findings suggest that ESM, through its major protein components such as LYZ, may serve as a promising dietary intervention for maintaining intestinal health and mitigating inflammation in the context of IBD.

An assay that integrates histidine-rich peptides (HisRPs) with high-affinity aptamers was developed enabling the specific and sensitive determination of the target lysozyme. The enzyme-like activity of HisRP is inhibited by its interaction with a target recognized by an aptamer. In the presence of the target, lysozyme molecules progressively assemble on the surface of HisRP in a concentration-dependent manner, resulting in the gradual suppression of enzyme-like activity. This inhibition of HisRP’s enzyme-like activity can be visually observed through color changes in the reaction product or quantified using UV-visible absorption spectroscopy. Under optimal conditions, the proposed colorimetric assay for lysozyme had a detection limit as low as 1 nM and exhibited excellent selectivity against other nonspecific interferents. Furthermore, subsequent research validated the practical applicability of the developed colorimetric approach to saliva samples, indicating that the assay holds significant potential for the detection of lysozymes in samples derived from humans. Graphical Abstract

Background and Aim: Immune-modulating molecules mainly act on innate immune cells, which are central to early defense against invading pathogens and contribute to developing adaptive immunity. Yeast-extracted [beta]-glucan, a model immune-modulating molecule, is widely used in several animal species; however, its effect on horse immune parameters has not been thoroughly investigated yet. This study aimed to evaluate the effects of orally administered [beta]-glucan on selected innate immune parameters in horses. Materials and Methods: Eighteen thoroughbred horses were assigned equally into three groups as follows: One control group (no [beta]-glucan) and two [beta]-glucan experimental groups (one received 125 mg and the other 2 g of [beta]-glucan per day for 28 days). Blood samples were collected before and at the end of the experiment for hematological analysis, whole blood phagocytosis, respiratory burst assays, and to assess the serum lysozyme and complement hemolytic activities. Results: At the end of the experiment, significant decreases (p<0.05) in monocyte numbers were observed in the control horses (258.8[+ or -]45.9 vs. 115.3[+ or -]41.5) and in those fed 125 mg/day of [beta]-glucan (208.8[+ or -]72.3 vs. 99.2[+ or -]60.7), whereas a significant increase in numbers was noted in the horses that were fed 2 g/day of [beta]-glucan (303.5[+ or -]45.8 vs. 429.8[+ or -]86.0; p<0.05). The natural hemolytic activity of the complement was higher only in horses fed 2 g/day of [beta]-glucan (p=0.018) compared to the other groups. The hemolytic activity in the classical pathway was higher in those fed 125 mg/day (p=0.0035) and 2 g/day of [beta]-glucan (p=0.0001). Conclusion: [beta]-glucan improves important innate immune parameters and might be fed to horses before stressful events. Keywords: animals, glucans, monocytes, muramidase.

The interactions between poly(acrylic acid) (PAA), poly(vinyl alcohol) (PVA), and lysozyme (Lys) in an aqueous environment at pHs of 2, 4, and 7.4 were discussed considering the experimental data obtained by turbidimetry, electrokinetic and rheological measurements, and FTIR analysis. It was found that the increase in PAA amount reduces the coacervation zone by shifting the critical pH[sub.cr1]to higher values while the critical pH[sub.cr2] remains unchanged. The coacervation zone extended from 3.1–4.2 to 2.9–4.7 increasing the Lys concentration from 0.2% to 0.5%. The zeta potential measurements showed that the PAA–PVA–Lys mixture in water is the most stable in the pH range of 4.5–8. Zero shear viscosity exhibited deviations from additivity at both investigated pHs, and a maximum value corresponding to a maximum hydrodynamic volume was revealed at PAA weight fractions of 0.4 and 0.5 for pHs of 4 and 7.4, respectively. The binding affinity to Lys of PAA, established by molecular dynamics simulation, was slightly higher than that of PVA. The more stable complex was PAA–Lys formed in a very acidic environment; for that, a binding affinity of −7.1 kcal/mol was determined.

Antibacterial lysozyme hydrogels show attractive advantages in wound dressings due to their intrinsic antibacterial activity and excellent biochemical and mechanical properties. Unfortunately, the development of such hydrogels is still greatly limited due to the lack of universal gelation strategies. Herein, a universal gelation strategy between lysozyme‐nanofiber (LZF) and inorganic salts is proposed for the first time to construct functional nanofibrous lysozyme‐based hydrogels. In particular, divalent anions are found to universally drive LZF for the aggregation and transformation into three‐dimensional nanofibrous network hydrogels via electrostatic interaction, and the key role of divalent anions in the gelation is further proved by molecular dynamics simulation. In addition, near‐infrared light‐mediated photothermal characteristics are endowed with LZF to enhance its inhibitory activity of multidrug‐resistant bacteria by the skeleton modification with genipin to produce genipin‐conjuagted LZF (GLZF). As a distinct application paradigm, the brilliant immunomemory MnSO4‐crosslinked GLZF hydrogel is constructed to sensitize the cGAS‐STING pathway and skillfully establish an antibacterial immune microenvironment. It can excellently realize the anti‐recurrence of diabetic wound infection via photo‐enhanced bacterial killing and the cGAS‐STING pathway. Thereby, it paves the way to employ the universal divalent anion‐mediated gelation strategy for the future development of functional inorganic salt hybrid lysozyme hydrogels. A universal gelation strategy is proposed to construct functional nanofibrous lysozyme‐based hydrogels via the electrostatic interaction between divalent anions and lysozyme‐nanofiber. As a distinct application paradigm, the MnSO4‐crosslinked nanofibrous lysozyme hydrogel is utilized to skillfully establish an antibacterial immune microenvironment, which excellently realizes the anti‐recurrence of diabetic wounds infection via photo‐enhanced bacterial killing and cGAS‐STING pathway.